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K J Lafferty

Publications and source records attributed to K J Lafferty.

At least 127 records · Page 7Linked to original sources
PubMed1980

Successful allotransplantation of mouse pancreatic islets to nonimmunosuppressed recipients.

Pancreatic islets from BALB/c (H-2d) mice are rejected within 14 days of transplantation to the kidney capsule of allogeneic, CBA/H (H-2k) recipients. Cyclophosphamide pretreatment of the islet donor reduced the intensity of the allograft response, and these islets undergo a more chronic rejection process. Islets from cyclophosphamide-pretreated donors can be cultured in a gas phase of 95% O2 and 5% CO2, provided the islets are aggregated into clusters of about 50 islets. After a culture period of 7--12 days, the islet tissue was transplanted to normal allogeneic recipients, where the tissue elicited little or no allograft response over a 3-mo observation period.

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PubMed1979

Generation of homogeneous populations of alloreactive T cells in vitro.

The supernatant from Con A-activated spleen cells (CS) can be used to generate homogenous populations of alloreactive T cells in vitro. Subculture of activated cells in CS containing medium is required for the continued proliferation and expression of effector activity. Prolonged subculture in CS containing medium does not result in indefinite growth and proliferation of alloreactive T cells. The activity in CS required to maintain cytotoxic cell growth is not species specific, and is therefore separable from the costimulator activity in CS required for the initiation of the T cell response to alloantigen; this latter activity is species specific.

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PubMed1979

Cytotoxic and proliferative lymphocyte responses to allogeneic and xenogeneic antigens in vitro.

In vitro lymphoproliferative responses to foreign histocompatibility antigens are phylogenetically restricted. Responses occur most readily to allogeneic or closely related xenogeneic leucocytes, but not to unrelated xenogeneic cells. Specific cytotoxic T cell responses to foreign histocompatibility antigens show the same phylogenetic restriction. This lack of xenoreactivity is not due to a lack of precursor cells for the xenoantigens; guinea-pig lymphocytes, although normally unresponsive to mouse antigens, have a similar precursor frequency for these antigens as do lymphocytes of allogeneic mouse strains. Specific cytotoxic responses of guinea-pig lymphocytes to mouse antigens can be generated if a factor released from con A stimulated guinea-pig spleen cells is added to the culture medium. The factor produced by con A-activated spleen cells (CS) is also phylogenetically restricted in its action; CS must be obtained from animals homologous with the donor of the responding lymphocytes.

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PubMed1979

A high frequency of cytotoxic precursor cells for a syngeneic tumour.

The average frequency of cytotoxic precursor cells in DBA/2 lymph node cell preparations reactive to the syngeneic tumour P815 has been determined as 1 in 2000. This frequency is similar to the precursor frequency for an allogeneic tumour EL-4. The normal lack of response of DBA/2 lymph node cells to the syngeneic tumour P815 in vitro cannot be attributed to a lack of cytotoxic precursor cells. We conclude that in this tumour-host system non-immunogenicity reflects a defect at the inductive step.

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PubMed1978

Cytotoxic T cell responses to a syngeneic tumour: conditions for primary activation in vitro.

Primary cytotoxic responses of DBA/2 lymph node cells to a syngeneic tumour (the mastocytoma P815) have been generated in vitro. The development of these responses is dependent on the addition of a soluble factor (CSCS) which is produced by concanavalin A-activated spleen cells. The response is mediated by T lymphocytes, can be detected at low effector to target cell ratios and is directed against P815 tumour-associated antigens.

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PubMed1978

Immunological induction of T lymphocytes: role of antigen and the lymphocyte costimulator.

In vitro T cell activation requires both antigen presentation and a second stimulus provided by the lymphocyte costimulator. Neither alone is sufficient to induce specific T cell activation. The S+ phenotype of stimulating cells is dependent on the metabolic activity of these cells. This finding is consistent with the notion that production and/or release of the costimulator is a function of metabolically active cells. The costimulator acts at an early stage of the interaction between lymphocyte and antigen, and the costimulator, or a separate maintenance factor, is required throughout the culture period for the expression of full cytotoxic activity. The lymphocyte costimulator is not strain specific but is phylogenetically specific. The activation of cytotoxic T cells by S+ cells is also phylogenetically specific, and this specificity of cellular activation can be accounted for by the species specificity of the lymphocyte costimulator.

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PubMed1977

Activation of cytotoxic T cells by nonstimulating tumor cells and spleen cell factor(s).

The ability of three cultured mouse tumor lines to stimulate a cytotoxic response in 5-day cultures of allogeneic lymph node cells was studied with a 51Cr release assay. Two lines of mesenchymal origin, P815 and EL-4, were found to be highly stimulatory, whereas the third cell line, CaD2, a mammary gland epithelial tumor, did not stimulate over a wide range of cell concentration. CaD2 cells were shown to contain major antigens similar to those of P815 cells by the specific lysis of both cells by lymphocytes activated to H-2d-bearing peritoneal cells.UV-irradiated P815-cells, like gamma-irradiated CaD2 cells, did not stimulate a cytotoxic response, but both cell lines were found to stimulate a full and specific response to allogeneic lymph node cells if these mixed cultures were supplemented with a supernatant harvested from concanavalin A-stimulated spleen cells.

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PubMed1977

The origin and mechanism of the allograft reaction.

Previous explanations for the allograft reaction have been based on the concept that antigen causes immunocyte activation, following engagement of the immunocyte's specific receptor. This notion lead to the concept of immune surveillance, the idea that the evolutionary pressure responsible for the development of the vertebrate immune system involved in allograft rejection was a need to recognize and destroy tumor cells that carried novel antigens. Allografts were rejected because they were, in effect, mistaken for tumor cells. At the practical level, these ideas suggested that a solution to the allograft problem required treatment of the recipient in a way that would reduce or eliminate the recipient's immune response to the grafted tissue. We have rejected these ideas on the grounds that the basic premise, the notion that antigen alone drives T cell differentiation, is invalid. To explain the origin of the allograft response, we have developed a theory of allogeneic reactivity based on the concept that a stimulator cell is required for the activation of blood cells involved in both nonspecific inflammatory reactions and specific cellular immunity. This theory provides a conceptual link between invertebrate and vertebrate alloreactivity and explains why the MHC and factors controlling the expression of T cell activity map in the same region of the genome. According to this theory, it is blood cells carried within the transplanted tissue and not transplantation antigen on the surface of graft parenchymal cells, that constitute the major barrier to allotransplantation. Experimentally we have presented evidence for a two-signal mechanism for T cell activation. Both antigen and an inductive stimulus are required for T cell activation, and neither factor alone induces detectable T cell activation. Organ culture of thyroid tissue for 4 weeks renders it non-immunogenic without altering its antigenic composition. Furthermore, cyclophosphamide pretreatment of the thyroid donor, a procedure that does not destroy the vascular bed of the donor tissue, also reduces its immunogenicity. These findings are of both theoretical and practical importance. They show that transplantation antigen carried on the parenchymal cells of a transplant do not constitute the major barrier to allotransplantation and, at least in the case of thyroid and parathyroid transplantation, indefinite allograft survival can be achieved by treatments directed at the transplanted tissue and not the recipient.

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PubMed1976

Activation of transplant immunity: effect of donor leukocytes on thyroid allograft rejection.

The survival of thyroid allografts in mice was prolonged by either holding the grafts in vitro culture for 20 to 27 days or by cobalt-60 irradiation of the donor 2 days before transplantation with or without the intravenous injection of colloidal carbon just before removing the thyroid from the donor. In both cases the rejection process was restored by an intravenous injection of recipients with living peritoneal exudate cells (50 to 80 percent macrophages) syngeneic to the thyroid donor.

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PubMed1976

Mechanism of thyroid allograft rejection.

Balb/c thyroids, held in organ culture for 26 days, survive and function as well as isografts for greater than 100 days in CBA recipients. Uncultured allografts are totally rejected by 20 days after transplantation. Prolonged allograft survival can also be achieved by the treatment of donor animals with cyclophosphamide prior to harvesting tissues for transplantation. These allografts do not survive as well as 26 day cultured allografts, but cyclophosphamide pretreatment reduces the culture time required to achieve indefinite survival to 7 days. The provision of an allogeneic (LD) stimulus by thyroid tissue that is I-region incompatible with the host does not facilitate the rejection of a tolerated cultured allograft. However, activation of the host immune system by an uncultured graft syngeneic to a tolerated cultured allograft leads to the chronic rejection of the cultured transplant. The transfer of a tolerated cultured allograft back to its strain of origin induces an acute inflammatory reaction that causes tissue damage within the transplant but does not lead to the total destruction of the tissue.

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PubMed1976

Effect of organ culture on the survival of thyroid allografts in mice.

Mouse thyroid can be maintained in organ culture for 4 weeks. Uncultured BALB/c thyroid is rejected 10-15 days after transplantation under the kidney capsule of H-2 disparate recipients (C57BL, CBA). Organ culture of thyroid tissue prior to transplantation prolongs allograft survival. This prolongation of graft survival increases with increasing time in culture and 80-90% of BALB/c thyroids maintained in culture for 26 days survive in allogeneic CBA recipients for a 60- to 70-day test period. These allografts show normal function as measured by 125I uptake, and show no histological evidence of chronic rejection. Cultured allografts can be rejected if the host's immune system is stimulated with viable leukocytes of donor origin. Host animals carrying a functioning allograft are not tolerant of donor tissues and will reject a second uncultured allograft from the same donor strain.

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